Hot flashes are prevalent with menopause and can significantly negatively impact a woman's life. Studies estimate as many as 80 percent of women report hot flashes. Besides being a physiologic phenomenon accompanied by heart palpitations and sweating, hot flashes can also be accompanied by negative emotions such as anxiety and panic. There are limited treatment options with respect to high efficacy and low side effect profile. The current nonhormonal options provide, at most, around 60 percent reduction in hot flashes which is lower than hormones. The goal of this research program is to find both pharmacologic and non-pharmacologic options for improvement in menopausal symptoms, including hot flashes. This pilot study will test the combination of a potentially effective behavioral (non-pharmacologic) intervention, hypnosis, with a known effective pharmacologic intervention, venlafaxine ER. Venlafaxine has been well studied and found to provide a 55 percent reduction in hot flashes. Hypnosis will be tested with both venlafaxine ER as well as a placebo pill. Likewise, we will utilize a control hypnosis comparison as well. The aims of this study are to evaluate the effect size of venlafaxine ER 75 mg with hypnosis compared to venlafaxine ER 75 mg with control hypnosis compared to placebo with hypnosis compared to placebo with control hypnosis, as well as to evaluate the side effects of each of these treatments. We will also evaluate potential moderating variables of expectancy and hypnotizability. The pilot study will randomly assign postmenopausal women reporting hot flashes to one of the four treatment arms described above for 8 weeks, including a baseline week. Hot flashes will be measured daily throughout the trial with a prospective daily diary, including the baseline week. Differences in hot flash reduction between baseline and the last week of treatment will be compared between each arm. Effect sizes and confidence intervals will be calculated. Questionnaires measuring secondary outcomes such as sleep, mood, hot flash interference and menopause related quality of life will be completed before starting the study interventions and at the end of the study. A larger, more definitive trial is planned based on the results and effect sizes of this pilot trial. PUBLIC HEALTH RELEVANCE: This project will be the first step to a larger study evaluating the combination of low dose venlafaxine (37.5 mg and 75 mg) with self-hypnosis for reducing hot flashes. This is a novel combination with the potential to reduce hot flashes equal to estrogen based therapy without significant unwanted side effects. The risk/benefit of estrogen therapy has recently been deemed negative with respect to hot flash management, yet hot flashes can significantly negatively impact one's life. Therefore, effective treatments without unwanted side effects are needed. The novelty of combining a pharmacologic with a non-pharmacologic intervention in a large clinical trial for hot flashes is unprecedented. This pilot study will provide the data to go forward with a large, definitive trial. In addition, information regarding moderating variables of expectancy and hypnotizability will be gained.